Comparative Efficacy and Safety of Steroidal and Non-Steroidal MRAs in Heart Failure

Background: Non-steroidal mineralocorticoid receptor antagonists (nsMRAs) have shown reduced incidence of hyperkalemia and renal dysfunction in comparison to steroidal mineralocorticoid receptor antagonists (sMRAs). However, their comparative efficacy in heart failure (HF) remains uncertain. We performed a network meta-analysis to evaluate this question. Research Question: Do nsMRAs have superior efficacy and safety compared with traditional sMRAs in patient with HF? Method: Randomized controlled trials (RCTs) comparing sMRAs, nsMRAs and placebo in adults with HF were identified and pooled using a Bayesian random-effects network meta-analysis. Risk ratios (RRs) for dichotomous outcomes, mean differences (MDs) for continuous outcomes were calculated with 95% credible intervals (CrIs). Surface under the cumulative ranking curve (SUCRA) values were used to compare clinical outcomes (mortality, HF hospitalization), quality-of-life related outcomes (improvement of New York Heart Association [NYHA] functional class and Kansas City Cardiomyopathy Questionnaire [KCCQ] score), and adverse events (hyperkalemia and worsening renal function). Result: Nineteen RCTs (N=17,558) contributed data. sMRAs ranked highest for reducing cardiovascular mortality (SUCRA 80.25%) compared with nsMRAs (SUCRA 52.55%). sMRAs also ranked highest across the other clinical outcomes and for the improvement of NYHA functional class (RR 1.59, 95% CrI 1.13-2.28) compared with nsMRAs and placebo. Conversely, SUCRA values of worsening renal function were 9.88%, 67.61% and 72.5% for sMRAs, nsMRAs and placebo, respectively, indicating higher probability of renal safety with nsMRAs, with ranking closer to placebo. While both MRA classes elevated the risk of hyperkalemia compared to placebo, nsMRAs demonstrated a greater risk (RR 2.21, 95% CrI 1.73-2.75; SUCRA 7.74%) than sMRAs (RR 1.93, 95% CrI 1.61-2.27; SUCRA 42.26%). Conclusion: sMRAs demonstrated superior clinical and quality-of-life related outcomes in comparison to nsMRAs, while nsMRAs ranked more favorably for the preservation of renal function, suggesting that nsMRAs can be considered for patients with increased risk of renal dysfunction.